The Reaction Chemistry of Superoxide Ion in Aprotic Media

24 The Reaction Chemistry of Superoxide Ion in Aprotic Media D O N A L D T. SAWYER, E D W A R D J. N A N N I , JR., and J U L I A N L . R O B E R T S , JR. Downloaded by PENNSYLVANIA STATE UNIV on May 10, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0201.ch024

University of California, Department of Chemistry, Riverside, C A 92521

Superoxide ion (O -) is a strong Brönsted base, an effective nucleophile, and a moderate one-electron reducing agent. In the presence of O - polychloro hydrocarbons, are rapidly degraded via a primary nucleophilic displacement of chloride ion; the relative S 2 second-order rate constants for the chloromethanes are CCl > CHCl > CH Cl > CH Cl , with an approximate value of 1300 M s for CCl in DMF at 25°C. Combination of O - with basic substrates such as hydrophenazines, reduced flavins, and hydroxylamine yields substrate oxidation products via direct transfer of one, two, or three hydrogen atoms to O - from the reduced substrate. Superoxide ion reacts with the cation radical of methyl viologen (MV ) via a primary radical-radical coupling process to yield a diamagnetic adduct. The latter decomposes, apparently via a peroxide intermediate, to products that may represent the biological toxins of methyl viologen. A similar radical coupling reaction occurs between a neutral flavin radical and O - to yield a flavoperoxide anion. The latter is an effective reaction mimic for flavοoxygenases. When O - and reduced tran sition metal ions are combined, an overall redox process occurs via either direct electron transfer or a series of disproportionation steps. The kinetics and mechanisms of these processes have been studied in relation to those for the superoxide dismutases. 2

2

N

4

3

3

2

2

-1 -1

4

2

2

+

2

2

I h e e l e c t r o n transfer r e d u c t i o n o f d i o x y g e n y i e l d s s u p e r o x i d e i o n ( 0 " ) as a p r i m a r y p r o d u c t i n b i o l o g i c a l ( I ) as w e l l as c h e m i c a l systems (2). T h i s redox process has b e e n c h a r a c t e r i z e d b y electro c h e m i c a l s t u d i e s i n a p r o t i c s o l v e n t s s u c h as d i m e t h y l f o r m a m i d e 2

0065-2393/82/0201-0585$06.00 © 1982 A m e r i c a n C h e m i c a l Society In Electrochemical and Spectrochemical Studies of Biological Redox Components; Kadish, K.; Advances in Chemistry; American Chemical Society: Washington, DC, 1982.

BIOLOGICAL REDOX COMPONENTS

586 (DMF)

(3) a n d b y p u l s e

radiolysis studies

m o l a l i t y as t h e s t a n d a r d state for 0 0

2

(4) (for

unit

0 ") 2

EDMF= - 0 . 6 0 V VS. N H E ] E° ' = -0.17 V J

+ e-*±(V

H

Downloaded by PENNSYLVANIA STATE UNIV on May 10, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0201.ch024

and

2

i n water

m U

j

2 0

F i g u r e 1 is a s u m m a r y o f t h e r e d u c t i o n p o t e n t i a l s for d i o x y g e n a n d its r e d u c t i o n p r o d u c t s i n a q u e o u s m e d i a for a c i d i c , n e u t r a l , a n d b a s i c conditions. T h e s e data represent a best estimate from the considera tion o f pulse radiolysis, electrochemical, spectrophotometry, and c a l o r i m e t r i c m e a s u r e m e n t s (4-9), and*are b a s e d o n ρ Κ v a l u e s o f 4 . 6 9 for H 0 · (4) a n d 11.9 for H O (8). α

2

2

z

T h e l i m i t e d lifetime o f superoxide ion i n aqueous solutions, b e c a u s e o f r a p i d h y d r o l y s i s a n d d i s p r o p o r t i o n a t i o n [(4) a n d F i g u r e 1], H Or

+

+ ( V Η0 ·

+ Η 0 · -* 0 2

2

20 - + 2 H 2

+

+ H0 "

2

Η 0 · + Η 0 · -» 0 2

pK

2

2

+ H 0 2

*± H 0 2

2

5

k

4

+ 0

2

(2)

= 1.0 x 1 0 M ^ s "

3

2

= 4.69 8

k

2

a

= 8.6 x 1 0 M ' V Kp„

7

= 4 x 10

1

(3)

1

(4)

2 0

(5)

p r o m p t e d n u m e r o u s i n v e s t i g a t i o n s o f its r e a c t i o n c h e m i s t r y i n a p r o t i c solvents. I n s u c h solvents (and i n the absence o f p r o t i c substrates a n d t r a c e l e v e l s o f m e t a l i o n s ) s u p e r o x i d e i o n is s t a b l e , w i t h a h a l f - l i f e o f m o r e t h a n 8 h at m i l l i m o l a r c o n c e n t r a t i o n s . T h e d i f f e r e n c e i n t h e r e d u c t i o n p o t e n t i a l s for d i o x y g e n i n n e u t r a l [ - 0 . 6 0 V vs. the normal h y d r o g e n electrode ( N H E ) ] a n d

acidified

(+0.12 V vs. N H E ) D M F p r o v i d e s an approximate m e a s u r e o f the a c i d i t y o f Η 0 · i n a p r o t i c m e d i a (pK 2

a

~ 13). H e n c e , s u p e r o x i d e i o n is a

stronger base i n D M F t h a n i n a q u e o u s m e d i a b e c a u s e o f the m u c h w e a k e r solvation o f anions b y aprotic solvents. For the same reason, the proton-driven disproportionation of superoxide

i o n ( E q u a t i o n 5) is

e v e n m o r e c o m p l e t e i n a p r o t i c s o l v e n t s a n d c a u s e s s u p e r o x i d e i o n to h a v e u n i q u e l y s t r o n g B r o n s t e d b a s i c i t y [ e . g . , 1 - b u t a n o l ( p K = 3 3 ) is a

d e p r o t o n a t e d b y s u p e r o x i d e i o n i n D M F ] (10). T h i s chapter s u m m a r i z e s the p r i m a r y reaction c h e m i s t r y o f superoxide ion i n aprotic solvents. T h e reactivity o f superoxide ion i n a q u e o u s m e d i a is e x p e c t e d t o b e s i m i l a r , b u t m o d e r a t e d b y t h e l e v e l i n g effects o f w a t e r a n d t h e c o m p e t i t i v e p r o t o n - i n d u c e d d i s p r o p o r tionation reactions. T h e latter process y i e l d s substrate anions, d i o x y gen, a n d h y d r o g e n p e r o x i d e . T h i s process, p l u s s i m i l a r reactions o f a c i d i c s u b s t r a t e s i n a p r o t i c s o l v e n t s , l e a d s to o x i d a t i o n s b y o x y g e n a n d h y d r o g e n p e r o x i d e o f substrate anions that w e r e e r r o n e o u s l y attri b u t e d t o d i r e c t e l e c t r o n t r a n s f e r to s u p e r o x i d e i o n (3).

In Electrochemical and Spectrochemical Studies of Biological Redox Components; Kadish, K.; Advances in Chemistry; American Chemical Society: Washington, DC, 1982.


5

-0.065

-H 0.12

Iι

+0.9

+ 0.401

+0.5

+ 0.815

L .

2

+ 0.35

-HO,

-1-0.5

J

2

H 0

+ 0.9 2

-

Ί

+0.867

HO + · 0

+ 0.65

2

_

+ 1.349

- H 0 + ·0Η-

+ 1.763

HoO + ·0Η-

+ 1.20

•1.3

+ 1.229

1 1

-HoO 2V2

+0.9

+ 1.44

0 ^ ^ 0 2 0 .

+0.281

+0.695

H0

-f 1.66

+1.3

+ 1.8

+ 2.2

2

2

•4

1

OH

-2H 0

1

H 0

-

7

p H 14 (1 M O H " )

pH

p H 0 (1 M H + )

Figure 1. Potentials for oxygen redox couples in aqueous media at 25°C; values represent standard re duction potentials vs. the NHE. The standard state for 0 is 1 atm.; a standard state of unit molality shifts the one-electron process by +0.17 V; the two-electron process by +0.085 V; the three-electron process by +0.06 V; and the four-electron process by +0.04 V.

1

-0.33

-0.33

-0.05

+ 1.4



588

Oxidation-Reduction Reactions One-Electron

Reductant.

0 /Or

T h e r e d o x p o t e n t i a l for t h e

2

c o u p l e i n d i m e t h y l f o r m a m i d e ( E q u a t i o n 1) is s u f f i c i e n t l y n e g a t i v e to m a k e s u p e r o x i d e a moderate r e d u c i n g agent. F o r e x a m p l e , d i s s o l v e d s u l f u r d i o x i d e is r e d u c e d b y s u p e r o x i d e i o n

Or + s o

2

«± 0

2

(11).

SOr

+

Ke = 5

(6)


T h e p r o c e s s , w h i c h is d r i v e n to t h e r i g h t b y t h e d i m e r i z a t i o n o f SOr dithionite ( K

to

3

d i m e r

= 5 x 1 0 ) , i n d i c a t e s t h a t s u p e r o x i d e i o n is a m o r e

effective one-electron r e d u c i n g agent than dithionite i n D M F . Other examples o f reductions b y superoxide ion i n c l u d e 3,5-dii-butyl-o-quinone ( D T B Q ) in D M F Or and

+ D T B Q «± D T B Q " + 0

numerous

transition

Cu(II)(9,10-phenanthroline) (TPP)Cl (15).

metal

K

2

= 0.8 x 1 0

7

complexes

(12),

in

(14),

(7)

aprotic

Cu(II)salicylate

( T P P is t e t r a p h e n y l p o r p h i n a t o )

6

solvents;

(13),

and

Mn(III)-

Fe(III)(TPP)Cl

I n aqueous m e d i a , superoxide i o n (generated b y pulse radioly

sis) r e d u c e s F e ( I I I ) ( E D T A ) (16) a n d f e r r i c y t o c h r o m e c cyt c ( F e

3 +

) + Or ^

R e c e n t s t u d i e s (18)

cyt c ( F e

2 +

) + O

K

z

8

(17).

= 4 χ 10

confirm that substantial a m o u n t s

4

(8)

of singlet

oxygen ( Ό ) result from the oxidation o f superoxide ion b y coordi 2

n a t e d saturated transition m e t a l oxidants ( w i t h Ε °'-values greater than +0.34 V ) i n D M F . Measurements of singlet oxygen b y photon count i n g i n d i c a t e a s i g n i f i c a n t y i e l d w h e n f e r r i c e n i u m p e r c h l o r a t e is t h e oxidant, but a n e g l i g i b l e amount from superoxide ion oxidation b y F e ( I I I ) ( C l 0 ) 3 . T h i s result c a n b e r a t i o n a l i z e d o n the basis that the 4

c o o r d i n a t e l y saturated f e r r i c e n i u m i o n forms a s i n g l e t transition-state c o m p l e x w i t h superoxide ion, [ ( C p ) F e : 0 : ] . Other oxidants 2

2

t r

that

c o n v e r t s u p e r o x i d e i o n to s i n g l e t o x y g e n i n c l u d e M n ( I I I ) ( 0 3 t e r p y )

3 + 2

( 0 t e r p y is 2 , 2 ' , 2 " - t e r p y r i d i n e Ι , Ι ' , Γ - t r i o x i d e ) a n d [ M n ( I V ) ( o - p h e n ) 3

0]

2

4 + 2

( o - p h e n is

1,10-phenanthroline).

O x i d a n t v i a H y d r o g e n - A t o m Transfer.

T h e results o f a

recent

i n v e s t i g a t i o n (19) d e m o n s t r a t e t h a t s u p e r o x i d e is a n e f f e c t i v e o x i d a n t o f basic r e d u c i n g substrates w i t h r e a d i l y transferable h y d r o g e n atoms. W h e n s u p e r o x i d e i o n is c o m b i n e d ( 1 : 1 m o l r a t i o ) w i t h e i t h e r d i h y d r o p h e n a z i n e o r N - m e t h y l h y d r o p h e n a z i n e ( b o t h m o d e l s for r e d u c e d flavins) i n d i m e t h y l f o r m a m i d e , a s t o i c h i o m e t r i c y i e l d o f p h e n a z i n e or JV-methylphenazine r a d i c a l , r e s p e c t i v e l y , results from a t w o - h y d r o g e n a t o m or a o n e - h y d r o g e n a t o m transfer


24.

Superoxide Ion in Aprotic Media

SAWYER ET AL.

phenH

2

+ 0 " + Hsol

589

phen + ^ (-sol) + H 0 + O H "

2

n

C H N p h e n H + 0 " - * C H N phen- + H 0 " 3

2

(9)

2

3

(10)

2

S i m i l a r r e a c t i o n s are o b s e r v e d for r e d u c e d flavins, h y d r o x y l a m i n e , a n d h y d r a z i n e . T h e stoichiometry o f the reactions

is c o n t r o l l e d b y

the

n u m b e r of r e d u c i n g h y d r o g e n atoms per substrate m o l e c u l e . C o n v e r s i o n o f s u c h h y d r o g e n a t o m s to p r o t o n s p r o v i d e s s t a b i l i z a t i o n o f t h e 2

2

reduction products of superoxide ion ( 0 ~ ,

O", and O ").

2


M o s t o f the r e p o r t e d oxidations o f p r o t i c substrates b y s u p e r o x i d e a c t u a l l y r e p r e s e n t a n i n i t i a l p r o t o n a b s t r a c t i o n to g i v e s u b s t r a t e a n i o n and disproportionation species, H 0

_ 2

and 0

2

(3). T h e l a t t e r o x i d i z e t h e

s u b s t r a t e a n i o n for c a t e c h o l s a n d α - t o c o p h e r o l . A l t h o u g h t h e s a m e p r o cess w a s s u g g e s t e d for t h e o x i d a t i o n o f a s c o r b i c a c i d (3), t h e t o t a l a b sence o f any intermediate 0 tion o f 0 " ) 2

a n d a 1:1

2

(from the p r o t o n - i n d u c e d d i s p r o p o r t i o n a

i n i t i a l r e a c t i o n s t o i c h i o m e t r y for t h e

0 "2

a c o r b i c a c i d r e a c t i o n to g i v e p r i m a r i l y ascorbate r a d i c a l a n i o n r e q u i r e a n a l t e r n a t i v e m e c h a n i s m . T h e s e factors a n d t h e r a p i d b i m o l e c u l a r k i n e t i c s (fc , 2

2.8 Χ 1 0

4

M

_ 1

s

_ 1

)

indicate that a concerted

hydrogen-

a t o m t r a n s f e r a n d p r o t o n t r a n s f e r to s u p e r o x i d e i o n f r o m a s c o r b i c a c i d o c c u r s (JO) CH OH 2

HCOH

/

Ο

CH OH 2

HCOH Ο

\

HC

C = 0 + Or

I I c—c I I OH

O H

Hjjasc

-> H C

/

\

C = 0 +

I I c—c I ^ ι

H 0 2

( I D 2

Ο ί- ) Ο asc"

f o l l o w e d b y a p r o t o n - i n d u c e d d i s p r o p o r t i o n a t i o n o f the ascorbate r a d i c a l a n i o n (asc") t o d e h y d r o a s c o r b i c a c i d ( d e h y d ) a n d a s c o r b a t e a n i o n (Hasc") H a s c + 2 a s c " -> d e h y d + 2 H a s c " 2

(12)

B o t h H a s c a n d a s c " a p p e a r to b e u n r e a c t i v e w i t h h y d r o g e n p e r o x i d e i n D M F a n d t h e r e is n o e v i d e n c e for a c o n c e r t e d t w o - h y d r o g e n a t o m transfer from H a s c to s u p e r o x i d e i o n . T h e f a c i l e o x i d a t i o n o f ascorbate i o n i n a q u e o u s m e d i a at p H 9.9 b y s u p e r o x i d e i o n [ g e n e r a t e d b y p u l s e r a d i o l y s i s (20)] p r o b a b l y o c c u r s v i a a s i m i l a r h y d r o g e n - a t o m t r a n s f e r 2

2


590


mechanism, as suggested previously (21). Hence, ascorbic acid ap pears to be unique among acidic substrates in its ability to reduce superoxide ion directly to hydrogen peroxide without significant con comitant proton-induced disproportionation.


Radical-Radical Coupling Combination of superoxide ion with the cation radical (MV"*") of methyl viologen (l,l'-dimethyl-4,4'-bipyridinium ion, paraquat) in D M F and D M S O results in a primary radical-radical coupling reac tion to yield a diamagnetic product (Figure 2). This conclusion is based on electrochemical, spectroscopic, N M R , electron paramagnetic reso nance (EPR), thin-layer chromatography (TLC), high performance liquid chromatography (HPLC), and mass spectrometric measure ments (22). Characterization of reaction intermediates and products provides the basis for proposing a self-consistent mechanistic scheme. This is the first definitive example of a radical reaction for superoxide ion.

MVt

(13) Ο

\

ΟΘ

[MV0 ] 2

IΝ — C H

CH —Ν 3

[MV0 ]

3

2

O-O H

-Jtr CH

3

0=C—Ν—CH=CH—C=< MV0

2

T T

N-CH

3

(14)

I °· polymer


SAWYER ET AL.

Superoxide

Ion in Aprotic

Media

591


24.

Ε, V vs. SCE Figure 2. Cyclic voltammograms in DMF (0.1 M tetraethylammonium perchlorate) of a, 1 m M Of; b, 1 m M methyl viologen cation radical (MV-); and c, 0.5 m M 0 " plus 0.5 raM M V within 5 min after mixing. Controiled-potential coulometry was used to prepare Ο ^ from 0 and MV from MVCl . Measurements were made with a Pt electrode (area, 0.23 cm ) at a scan rate of 0.1 V/s (22). f

2

2

2

2

2



592

Resonance stabilization apparently precludes significant radical c o u p l i n g at t h e C - 4 p o s i t i o n . S u c h a p r o c e s s w o u l d l e a d to a s y m m e t r i c a l d i o x e t a n e i n t e r m e d i a t e a n d d i s s o c i a t i o n to t w o 4 - N - m e t h y l p y r i d o n e m o l e c u l e s ; o n l y t r a c e l e v e l s are d e t e c t e d i n t h e p r o d u c t s o l u t i o n . I n t h e p r e s e n c e o f D M S O o r o t h e r s u b s t r a t e s s u b j e c t to o x y g e n a tion b y peroxides, [ M V 0 ] undergoes such reactions before it can form t h e d i o x e t a n e i n t e r m e d i a t e a n d p r o d u c t s o f E q u a t i o n 14.


2

[MV0 ] + DMSO-> 2

DMSO

+ CH -NV-/0N-CH 3

3

(15)

ο [MVO] The

[ M V O ] species can

epoxide

r e a r r a n g e to a l a c t a m , h y d r o l y z e

to a g l y c o l , a n d

r e a c t w i t h d i o x y g e n to g i v e a

v i a an

pyridone

+

(MVO )

[MVO]

CH —^— F l E t O O " 2

T h i s r e a c t i o n r e p r e s e n t s a s e c o n d e x a m p l e o f s u p e r o x i d e i o n a c t i n g as a c o u p l i n g reagent w i t h stable radicals. T h e neutral radical ( F l E t ) can b e p r o d u c e d from the one-to-one c o m b i n a t i o n o f F l E t a n d 0 " , or b y e l e c t r o c h e m i c a l r e d u c t i o n o f F l E t . T h e 4 a - F l E t O O ~ s p e c i e s , a n effec t i v e r e a c t i o n m i m i c for flavomonooxygenases (24), r e a d i l y o x y g e n a t e s d i m e t h y l s u l f o x i d e ( D M S O ) a n d other substrates subject to o x y g e n atom a d d i t i o n from p e r o x i d e ions. T h e r e s u l t i n g p s e u d o base, 4aF l E t O " , r e v e r t s to F l E t a n d H 0 u p o n a d d i t i o n o f p r o t o n s , o r is o x i d i z e d b y any residual oxygen. +

2

+

+

2

I n s p i t e o f v i g o r o u s a n d p e r s i s t e n t r e s e a r c h effort (3, 25-27), s u p e r o x i d e i o n has n o t b e e n f o u n d to a c t as a n i n i t i a t o r o f r a d i c a l c h a i n r e a c t i o n s . R a d i c a l - r a d i c a l c o u p l i n g o n l y is o b s e r v e d for t h o s e f o r c i n g c o n d i t i o n s ( M V * or F l E t ' p l u s s u p e r o x i d e i o n ) w h e r e a l t e r n a t i v e r e a c t i n s o f s u p e r o x i d e i o n are n o t f a v o r e d .



594


8,000 h

300

400

500

λ (nm) Figure 3. Absorption spectra in DMF (0.1 M tetraethylammonium perchlorate) of a, 0.5 m M N -ethyl-4a-hydroperoxy-3-methyllumiflavin (FlEtOOH); b, 0.52 mM FlEtOOH plus 0.52 mM t-BuO~K ; and c, 0.49 mM FlEt plus 1.15 mM 0 - (23). 5

+

+

2

Nucleophilicity Peroxide

and Monooxygenase

Reactivity

by

Intermediates

A l k y l H a l i d e s . U n d e r a p r o t i c c o n d i t i o n s , s u p e r o x i d e i o n attacks a l k y l h a l i d e s v i a n u c l e o p h i l i c s u b s t i t u t i o n (28). K i n e t i c s t u d i e s (2932) c o n f i r m t h a t t h e r e a c t i o n i s first o r d e r i n s u b s t r a t e a n d first o r d e r i n s u p e r o x i d e i o n , t h a t t h e rates f o l l o w t h e o r d e r 1 ° > 2 ° » 3 ° a n d I > B r > C I , a n d that the attack b y s u p e r o x i d e i o n results i n i n v e r s i o n of configuration. I n aprotic solvents, p r i m a r y a n d secondary a l k y l halides y i e l d dialkyl peroxides w h e n c o m b i n e d w i t h excess s u p e r o x i d e i o n (31-33), w h i c h is c o n s i s t e n t w i t h a m u l t i s t e p m e c h anism R X + 0 " -> R 0 2

RO

z

+ ( V

+ X "

2

R0 " + 0 2

(19) 2

R 0 " -I- R X — > R O O R + Χ " 2

(20) (21)

T h e p r i m a r y step occurs v i a a n S 2 displacenent o f h a l i d e from the c a r b o n . T h e r e s u l t i n g p e r o x y r a d i c a l is r e d u c e d b y a s e c o n d s u p e r N


SAWYER ET A L .

24.


595

o x i d e i o n t o g i v e t h e a l k y l p e r o x i d e i o n , w h i c h acts as a n u c l e o p h i l e for a t t a c k o f a s e c o n d s u b s t r a t e m o l e c u l e . I n D M S O (or i n t h e p r e s e n c e o f o t h e r r e a c t i v e s u b s t r a t e s ) R e a c t i o n 2 0 is f o l l o w e d b y a t t a c k o f t h e s o l v e n t b y R 0 ~ t o g i v e d i m e t h y l s u l f o n e 2

a n d a l c o h o l s (30, 3 4 , 3 5 ) R0

_ 2

+ DMSO -» D M S 0

+ RO"

2

(22)


A r e c e n t i n v e s t i g a t i o n (36) h a s d e m o n s t r a t e d t h a t p o l y c h l o r o h y d rocarbons ( C C 1 , CHCI3, C H C 1 , a n d p , p ' - D D T ) are r a p i d l y d e g r a d e d 4

2

2

by superoxide ion i n aprotic m e d i a ( D M F a n d D M S O ) . T h e primary step appears to b e a n u c l e o p h i l i c or c o n c e r t e d r e d u c t i v e d i s p l a c e m e n t o f c h l o r i d e i o n . K i n e t i c s t u d i e s c o n f i r m t h a t t h e i n i t i a l s t e p is r a t e l i m i t i n g a n d first o r d e r w i t h r e s p e c t t o s u p e r o x i d e i o n a n d s u b s t r a t e . T h e o v e r a l l r e a c t a n t a n d p r o d u c t s t o i c h i o m e t r i e s for t h e d e g r a d a t i o n o f the p o l y c h l o r o m e t h a n e s a n d ρ , ρ ' - D D T i n D M F are s u m m a r i z e d i n T a b l e I. I n a d d i t i o n , t h e s e c o n d - o r d e r rate constants for t h e p r i m a r y - 1

process are t a b u l a t e d ; the v a l u e o f 1300 M

s

_ 1

for C C 1 is t h e fastest 4

d i s p l a c e m e n t y e t o b s e r v e d for s u p e r o x i d e . C o m b i n a t i o n o f C C 1 w i t h six equivalents o f oxygen i n D M S O 4

y i e l d s a p r o d u c t s o l u t i o n t h a t , after d i l u t i o n w i t h w a t e r , c a n b e t i t r a t e d w i t h a q u e o u s H C 1 . T h e r e s u l t i n g t i t r a t i o n c u r v e is c o n s i s t e n t w i t h t h a t for a n a u t h e n t i c s a m p l e o f c a r b o n a t e i o n i n t h e s a m e m e d i u m . B e c a u s e p e r o x i d e s o x y g e n a t e D M S O t o i t s s u l f o n e (37), a r e a s o n a b l e c o n c l u s i o n

Table I.

Stoichiometries and Kinetics for the Reaction of 0 " with Polychloromethanes and p,p ' - D D T in D M F (0.1 M Tetraethylammonium Perchlorate) at 25°C 2

ci-

Substrate (S), 0.1-5 mM CH3CI CH C1 CHCI3 2

Of per S

released per S

1 2 4

1 2

2

eel*

2

9

3 4

6 3

p,p'-DDT

k , M~'s 80 460 1300 130

2

Overall Reactions: (a) (b) (c) (d) (e)

C H 3 C I + ( V -»· i C H O O C H + C I " + i 0 C H C 1 + 2 C V -*· C H 0 + 2 C 1 ~ + | 0 C H C 1 + 4 ( V -> H C ( 0 ) O Q - + 3 C 1 ~ + f 0 C C 1 + 6 C V -> C O / " ^ 4 C 1 - + 4 0 ρ , ρ ' - D D T + 3 0 Γ - * products + 2C1" + f O 3

2

2

3

2

2

2

3

4

2

2

;



596 is t h a t t h e

overall product from

s u p e r o x i d e i o n is C 0

2 4

the

reaction o f C C 1 w i t h

excess

4

" a n d t h a t i t r e a c t s w i t h t h i s s o l v e n t to y i e l d

CO3 -. 2

W h e n C H C I 3 is c o m b i n e d w i t h f o u r e q u i v a l e n t s o f s u p e r o x i d e i o n i n D M F , a b a s i c p r o d u c t s o l u t i o n is o b t a i n e d t h a t h a s t h e c h a r a c t e r i s t i c s o f p e r o x y f o r m a t e i o n (the a c i d i f i e d p r o d u c t s o l u t i o n o x i d i z e s I " to

h). O n the basis o f these e x p e r i m e n t s a n d the reaction s t o i c h i o m e


tries,

overall

reactions

are

proposed

for

the

degradation

of

the

p o l y c h l o r o s u b s t r a t e s (see T a b l e I ) . A s e l f - c o n s i s t e n t set o f r e a c t i o n s for the s u p e r o x i d e - c a r b o n tetrachloride system illustrates the m e c h a n i s t i c p r o c e s s e s for t h i s c l a s s o f s u b s t r a t e s . CC1

4

+ 0 - -> [ C C l ( 0 - ) ] 2

4

CC1 0 3

3

3

3

4

+ 2 O r -> 2 0

2

3

^ CC1 0

t r

+ O r -> C C 1 0 - + 0

CC1 0 - + CC1 3

CCl OOCCl

2

2

2

CCl OOCCl 3

2

+ CI"

2

(23) (24)

2

+ CI"

3

(25)

+ 2 CC1 0-

(26)

3

I C C 1 0 + O r -> C C 1 ( 0 ) 0

2

general

2

—>2

CC1 0 + 2 C l 2

+ Cl~

(27)

Lo i>cci(o)or + o 2

2

C C 1 ( 0 ) 0 " + C C 1 0 -> C C l ( 0 ) O O C C l ( 0 ) + CI" 2

2

C C l ( 0 ) O O C C l ( 0 ) + 2 Or

2 CC1(0)0" + 2 0 I——>2 C O

C0

2

+ 2 θ Γ - ^ C0

2 4

" + 0

z

(28) (29)

2

+ 2C l -

(30)

2

T h e peroxide intermediates o f Reactions 24, 27, a n d 30 can participate in monooxygenase

reactions

i n the presence

o f substrates s u c h

as

DMSO. Esters.

A n o t h e r d i m e n s i o n o f the n u c l e o p h i l i c i t y o f superoxide

i o n is its a b i l i t y to a t t a c k t h e c a r b o n y l c a r b o n o f esters to y i e l d c a r b o x y l i c a c i d a n i o n s a n d a l c o h o l s (38-40),

a n d to attack the c a r b o n y l

c a r b o n o f a c y l h a l i d e s to y i e l d d i a c y l p e r o x i d e s (41).

T h e ester h y

drolysis occurs v i a a c y l o x y g e n scission on the basis o f c o m p l e t e reten tion o f configuration i n the alcohol m o i e t y from an optically active ester

(38).

F o r the reaction o f s u p e r o x i d e i o n w i t h e t h y l acetate a n d p h e n y l a c e t a t e i n p y r i d i n e , t h e s e c o n d - o r d e r rate c o n s t a n t s a r e 0 . 0 1 1 a n d 160 M ^ s

- 1

M " ^ "

1

4

, r e s p e c t i v e l y (40). T h i s r a t i o o f r a t e c o n s t a n t s ( 1 0 ) is

c o n s i s t e n t w i t h o t h e r d a t a for t h e r e a c t i o n s o f p h e n y l a n d e t h y l e s t e r s w i t h e f f e c t i v e n u c l e o p h i l e s (42, 43), a n d w i t h a n S 2 m e c h a n i s m . T h e N


24.

SAWYER ET A L .


597

p r i m a r y r e a c t i o n a p p e a r s to b e a n u c l e o p h i l i c a d d i t i o n t h a t is f o l l o w e d b y e l i m i n a t i o n at t h e c a r b o n y l c a r b o n Ο

(40)

Ο"

Ο

I

Il

II

R—C—OR' + O rfcfR—C—OR' -* R—C

I

o-o

\

+ OR'

(31)

o-o


w i t h s u b s e q u e n t s t e p s to g i v e a n o v e r a l l e s t e r h y d r o l y s i s r e a c t i o n . Ο

Ο

Il

II

RCOO Ο

II

+ 0 < f -> R C O O " + 0 Ο

Ο

II

II II

RCOO" + RCOR' Ο

II

(32)

2

Ο

RCOOCR + "OR'

Ο

(33)

Ο

II

II

RCOOCR +

20

2RCO" + 20

2

(34)

A d d i t i o n o f s u p e r o x i d e i o n to a - k e t o - , α - h y d r o x y - , a n d α - h a l o c a r b o n y l c o m p o u n d s results i n a n u c l e o p h i l i c a d d u c t o f the c a r b o n y l c a r b o n , w h i c h u n d e r g o e s a n o x i d a t i v e c l e a v a g e to g i v e the c a r b o x y l i c a c i d that is d e r i v e d f r o m t h e a - p o s i t i o n (44). A g a i n , t h e p e r o x y a c i d a n i o n i n t e r m e d i a t e s ( E q u a t i o n 32) r e p r e s e n t e f f e c t i v e m o n o o x y g e n a s e s for s u b strates s u c h as D M S O . A g e n e r a l characteristic o f the n u c l e o p h i l i c attack o f a l k y l h a l i d e s a n d esters b y s u p e r o x i d e i o n is t h a t a p e r o x y r a d i c a l is t h e i n i t i a l p r o d u c t . T h i s p e r o x y r a d i c a l is r a p i d l y r e d u c e d b y a s e c o n d s u p e r o x i d e ion to a p e r o x i d e a n i o n , w h i c h c a n oxygenate s u s c e p t i b l e substrates. H e n c e , t h e n u c l e o p h i l i c i t y o f s u p e r o x i d e i o n p r o v i d e s a m e a n s to a c t i vate the r e d u c t i o n p r o d u c t o f d i o x y g e n to o r g a n o p e r o x y r a d i c a l s a n d organoperoxide ions. T h i s a b i l i t y m a y represent a significant hazard i n b i o c h e m i c a l systems.

Metal-Catalyzed Disproportionation M e t a l c a t i o n s c a n a c t as L e w i s a c i d s a n d t h r o u g h c h a r g e n e u t r a l i z a t i o n c a n b r i n g a b o u t the d i s p r o p o r t i o n a t i o n o f s u p e r o x i d e i o n to d i o x y g e n a n d a m e t a l p e r o x i d e (45). C o m b i n a t i o n o f s u p e r o x i d e i o n w i t h Zn(C10 )2, C d ( C 1 0 ) , a n d F e ( C 1 0 ) results i n s u c h a process. F o r M n ( C 1 0 ) a n d C o ( C 1 0 ) the resultant m e t a l p e r o x i d e s are u n s t a b l e a n d u n d e r g o f u r t h e r d i s p r o p o r t i o n a t i o n . A p l a u s i b l e m e c h a n i s m is o u t 4

4

2

4

2

4

2

4



598

l i n e d for m a n g a n e s e ( I I ) t o i l l u s t r a t e t h e r i c h v a r i e t y o f r e a c t i v e i n t e r mediates Mn

2 +

+ ( V

Mn(II)(Or)+ + O r - * [ 0

2

Mn(II)((V)

:Mn(II) :0

2

2

Mn(II)(0 ") + Mn(II)(0 -) 2

2

Mn(II) + 0 Mn(III)(Or )

2 +

2

^

+ Mn(II)

2

] -> 0

+

(35) 2

2

+ Mn(II)(0 -) 2

2 Mn(II)0 + 0

Mn(III)(Or )

(36) (37)

2

2+

(38)

[Mn(III)-0-0-Mn(III)]

4 +

(39)


4

[ Μ η ( Π Ι ) - 0 - 0 - Μ η ( Ι Ι Ι ) ] + + Mn(II)-> [Mn(III)-0-Mn(III)] [Mn(III)0]

2 +

4 +

+ [Mn(III)0]

+ Mn(II)^ [Mn(III)-0-Mn(III)l

2 +

4 +

(40) (41)

C l e a r l y , m a n y o f these i n t e r m e d i a t e s c a n o x i d i z e a n d oxygenate v a r i ous organic functional groups. T h e chemistry o f E q u a t i o n s 3 5 - 4 1 rep r e s e n t s a l i k e l y m e c h a n i s m for t r a n s i t i o n - m e t a l a c t i v a t i o n o f d i o x y g e n , e s p e c i a l l y w i t h r e s p e c t t o r a n c i d i f i c a t i o n o f fats a n d o i l s . A s m e n t i o n e d , s u p e r o x i d e i o n is a n e f f e c t i v e o n e - e l e c t r o n r e d u c t a n t for t r a n s i t i o n - m e t a l i o n s . U n d e r l i m i t e d c o n d i t i o n s , s u p e r o x i d e i o n a l s o c a n a c t as a n o x i d a n t o f r e d u c e d t r a n s i t i o n - m e t a l i o n s . T h e p r o c e s s must b e a u g m e n t e d through the formation o f a stable m e t a l - p e r o x i d e intermediate. Examples include Fe(II)ethylenediaminetetraacetic a c i d ( E D T A ) i n a q u e o u s m e d i a (46) a n d i r o n ( I I ) t e t r a p h e n y l p o r p h y r i n i n a p r o t i c m e d i a (15). S u c h r e a c t i o n s a r e a n e s s e n t i a l p a r t o f t h e f a v o r e d m e c h a n i s m s f o r t h e s u p e r o x i d e d i s m u t a s e ( S O D ) e n z y m e s (47). T h e F e ( I I I ) E D T A s y s t e m (48) r e p r e s e n t s a n e f f e c t i v e m o d e l for S O D i n a q u e o u s m e d i a ; t h e p r o p o s e d m e c h a n i s m is F e ( I I I ) E D T A + O r -> F e ( I I ) E D T A + 0 F e ( I I ) E D T A + Or ^

(42)

2

Fe(III)EDTA + H O 2

(43)

z

T h e bis(8-quinolinato)manganese(II) c o m p l e x [Mn(II)(8-Q) (H 0) ] a l s o is a n e f f e c t i v e c a t a l y s t for t h e d i s p r o p o r t i o n a t i o n o f s u p e r o x i d e i o n i n a p r o t i c m e d i a ( 4 9 ) , a n d h a s b e e n s u g g e s t e d as a n e f f e c t i v e m o d e l for t h e m a n g a n e s e S O D e n z y m e s (50). A r e a s o n a b l e m e c h a n i s m for t h e M n ( I I ) ( 8 - Q ) ( H 0 ) c a t a l y z e d d i s p r o p o r t i o n a t i o n o f s u p e r o x i d e ion involves a M n ( I I I ) - p e r o x i d e intermediate, w h i c h should b e a n effective o x i d a n t for s u p e r o x i d e i o n . 2

2

2

2

2

M n ( I I ) ( 8 - Ç ) ( H 0 ) + O r — M n ( I I I ) ( 8 - Q ) ( 0 H ) ( H 0 ) + OH" (44) 2

2

2

2

Mn(III)(8-Q) (0 H)(H 0) + 2

2

2

2

2

O r - ^ Mn(II)(8-Ç) (H 0) 2

2

2

+ 0

2

+ HOr

(45)

T h i s m e c h a n i s m is a r e a l i s t i c m o d e l for the m a n g a n e s e - S O D , i r o n S O D , a n d c o p p e r - z i n c - S O D enzymes.


24.

SAWYER ET AL.


599


Summary Superoxide is a versatile reactant, but its most dominant charac teristic is as an effective Bronsted base. It readily removes protons from water and weakly acidic substrates such as 1-butanol, and in so doing it disproportionates to yield peroxide and dioxygen. Under apro tic conditions, its strong basicity causes superoxide ion to act as a powerful nucleophile (probably second only to fluoride ion). Superoxide ion also is a moderate, but facile, one-electron reductant (about as effective as dithionite). Strong one-electron oxidants with closed coordination spheres (e.g., ferricenium ion) oxidize superoxide ion to singlet oxygen. Reduced transition-metal ions are oxidized by superoxide ion when their oxidized state forms stable peroxide adducts. Basic reductants such as dihydrophenazine, dihydroflavins, hydroxylamine, and hydrazine are oxidized by a hydrogen-atom trans fer mechanism. The only example of any radical character for superoxide ion is the formation of a diamagnetic adduct with reduced methyl viologen cation radical via a radical-radical coupling mech anism. Acknowledgment This work was supported by the National Science Foundation under Grant No. CHE79-22040. Literature

Cited

1. McCord, J. M.; Fridovich, I. J. Biol. Chem. 1969, 244, 604. 2. Wilshire, J. P.; Sawyer, D. T. Acc. Chem. Res. 1979, 12, 105. 3. Nanni, E .J.,Jr.; Stallings, M. D.; Sawyer, D. T.J.Am. Chem. Soc. 1980, 102, 4481. 4. Bielski, Β. H.J.Photochem. Photobiol. 1978, 28, 645. 5. Fee, J. Α.; Valentine, J. S. In "Superoxide and Superoxide Dismutase"; Michelsen, A. M.; McCord, J. M.; Fridovich, I., Eds.; Academic: New York, 1977; pp. 19-20. 6. Latimer, W. M. "Oxidation Potentials," 2nd ed.; Prentice-Hall: New York, 1952. 7. George, P. In "Oxidases and Related Redox Systems"; King, T. E.; Mason, M. E.; Morrison, M., Eds.; Wiley: New York, 1965; pp. 3-36. 8. Hoare, J. P. In "Oxidation-Reduction Potentials of Aqueous Solutions: A Selective and Critical Source Book"; Bard, A. J.; Parsons, R.; Jordan, Jr., Eds.; Int. Union Pure Appl. Chem., 1981; Chap. 4, in press. 9. Koppenol, W. H. Nature 1976, 262, 420. 10. Chin, D.-H.; Chiericato, G., Jr.; Nanni, E . J., Jr.; Sawyer, D. T., J. Am. Chem. Soc. 1982, 104, 1296. 11. Stallings, M. D.; Sawyer, D. T. J. Chem. Soc., Chem. Comm. 1979, 340. 12. Valentine, J. S.; Curtis, A. B. J. Am. Chem. Soc. 1975, 97, 224. 13. O'Young, C.-L.; Lippard, S. J. J. Am. Chem. Soc. 1980, 102, 4920. 14. Valentine, J. S.; Quinn, A. E . Inorg. Chem. 1976, 15, 1997. 15. McCandlish, E.; Miksztal, A. R.; Nappa, M.; Spenger, A. Q.; Valentine, J. S.; Strong, J. D.; Spiro, T. G.J.Am. Chem. Soc. 1980, 102, 4268.



600


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The Reaction Chemistry of Superoxide Ion in Aprotic Media

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